Mammals require molecular oxygen for essential metabolic processes including e.g. oxidative phosphorylation in which oxygen serves as electron acceptor during ATP formation. The lack of oxygen is not tolerated and mammals including humans are critically dependent on the oxygen supply by lungs. Therefore, intubation and mechanical ventilation represent one of the most widely used prophylactic and therapeutic clinical interventions to counteract the insufficient pulmonary oxygen-delivering capacity of patients who suffer from severe lung inflammation or other pathologies.
Many clinical conditions, including aspiration, trauma, and hemorrhagic shock are frequently followed by pulmonary and systemic infectious and septic complications that lead to pulmonary dysfunction and subsequent lung failure. Acute lung injury (ALI) or its more severe form, the Acute Respiratory Distress Syndrome (ARDS) occur with a frequency of approximately 130,000 cases and more than 50,000 deaths from ARDS per year only in the United States.
Although the majority of patients respond well to oxygen therapy with oxygen toxicity being an uncommon occurrence in intensive care medicine, there still remains the possibility that oxygen therapy may be suboptimal in ARDS patients as it may promote deleterious pulmonary inflammation, which fuels this disease process. Since the magnitude and duration of lung inflammation was shown to determine the final outcome of ARDS patients, it is important to avoid the possible adverse effects of oxygen on inflammatory processes. Day Y J, Marshall M A, Huang L, McDuffie M J, Okusa M D and Linden J. Protection from ischemic liver injury by activation of A2A adenosine receptors during reperfusion: inhibition of chemokine induction, Am J Physiol Gastrointest Liver Physiol, 286: G285-G293, 2004; Sullivan G W, Lee D D, Ross W G, DiVietro J A, Lappas C M, Lawrence M B and Linden J. Activation of A2A adenosine receptors inhibits expression of {alpha}4/{beta}1 integrin (very late antigen-4) on stimulated human neutrophils, J Leukoc Biol, 75: 127-134, 2004; Day Y J, Huang L, McDuffie M J, Rosin D L, Ye H, Chen J F, Schwarzschild M A, Fink J S, Linden J and Okusa M D. Renal protection from ischemia mediated by A2A adenosine receptors on bone marrow-derived cells, J Clin Invest, 112: 883-891, 2003; and Platts S H, Linden J and Duling B R. Rapid modification of the glycocalx caused by ischemia-reperfusion is inhibited by adenosine A2A receptor activation, Am J Physiol Heart Circ Physiol, 284: H2360-H2367, 2003.